Open AccessRB depletion is required for the continuous growth of tumors initiated by loss of RB
Author(s) -
Alex Doan,
Julia Arand,
Diana Gong,
Alexandros P. Drainas,
Yan Ting Shue,
Myung Chang Lee,
Shuyuan Zhang,
David M. Walter,
Andrea C. Chaikovsky,
David M. Feldser,
Hannes Vogel,
Lukas E. Dow,
Jan M. Skotheim,
Julien Sage
Publication year - 2021
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1009941
Subject(s) - biology , cancer research , genetics , microbiology and biotechnology
The retinoblastoma (RB) tumor suppressor is functionally inactivated in a wide range of human tumors where this inactivation promotes tumorigenesis in part by allowing uncontrolled proliferation. RB has been extensively studied, but its mechanisms of action in normal and cancer cells remain only partly understood. Here, we describe a new mouse model to investigate the consequences of RB depletion and its re-activation in vivo . In these mice, induction of shRNA molecules targeting RB for knock-down results in the development of phenotypes similar to Rb knock-out mice, including the development of pituitary and thyroid tumors. Re-expression of RB leads to cell cycle arrest in cancer cells and repression of transcriptional programs driven by E2F activity. Thus, continuous RB loss is required for the maintenance of tumor phenotypes initiated by loss of RB, and this new mouse model will provide a new platform to investigate RB function in vivo .